tbuckley/cabot-search huggingface dataset:
Abstract 10094: Perception of Cardiovascular Disease in Female Health Care Workers and Urgent Opportunity Gaps for Health Promotion
Authors: Johannes Bargehr, Jenny Jia Ling Cao, Zia Mehmood, Jonathan Evans, Omar Aglan, May Lwin, Rebecca Schofield
Journal: Circulation (2022)

Introduction: Cardiovascular disease (CVD) is the largest killer in women worldwide, yet minority of GPs and less than 50% of Cardiologists feel well prepared for risk assessment in women. Women have historically been under-represented in many major CV clinical trials. The percentage of women identifying CVD as leading cause of death (LCOD) has declined from 64% in 2009 to 43% in 2019, according to surveys in the United States. In 2020, we conducted the largest single-centre survey in the United Kingdom to explore the perceptions of CVD in female healthcare workforce in North-West Anglia NHS Foundation Trust. Methods: In September 2020, a total of 620 female healthcare workers in our institute completed an online questionnaire on health concerns, LCOD in women, screening/risk factors for CVD, and perceived personal risk status. There were 21 questions containing binary, ranked and best single choice answers which took approximately 15-minutes to complete. Results: Only 51% respondents were aware of CVD as the LCOD in women and 37% correctly identified lifetime incidence of CVD as one-in-three. Sixty-five percent believed to be at risk of CVD but only 18% had CVD as their biggest health concern. Three-quarters correctly identified CVD risk factors, but 74%, 59% and 40% were not aware of their cholesterol, diabetic status and BP, respectively. CVD screening was deemed necessary aged more than 40 by 31%, and aged more than 50 by 40%. Ninety-percent had never been screened for CVD. One-in-two believed a woman was more likely to survive a heart attack at the age of 60 compared to a man of similar age. Only 12% correctly indicated that BP below 120/80mmHg was normal and 57% were not aware of effects of HRT on CVD. Lastly, 82% did not feel well informed about their CV health. Conclusions: The survey did not include baseline demographics to associate age and social/ethnical background with the responses, nevertheless, there are significant gaps in knowledge and misconception about CVD in women among female healthcare workers. This study highlights opportunities for urgent education to bring more screening programmes into practice through major stakeholders i.e. local councils, GPs and Cardiologists.
Abstract 10604: Critical Role of Cardiac Imaging of Mechanical Complication in ST Elevation Myocardial Infarction: Left Ventricular Free Wall Rupture Diagnosed With CTA and Echocardiography
Authors: Caroline Lombardo, Christopher Lee, Eunjung Choi, Heather Kuhlman, Cynthia C Taub, Stanislav Henkin, Salvatore P Costa
Journal: Circulation (2022)

Case Presentation: An 81-year-old male with a thymoma (treated with surgery including partial pericardiectomy 25 years prior) presented to his local ER with chest pain radiating to his back. Vital signs were stable. EKG showed ST elevations in the lateral leads with Q waves. Troponin was positive. Diagnosis included STEMI as well as possible aortic dissection. CT angiography (CTA) did not show dissection; however, contrast extravasation and left ventricular (LV) free wall rupture was noted. Patient was not given thrombolysis and transferred for tertiary care. On arrival, the patient was pain free, hemodynamically stable, and an echo was obtained. Color Doppler and echo contrast confirmed a LV outpouching along the lateral wall with a “narrow neck” consistent with a pseudoaneurysm (PsA, figure 1). CT surgery declined an emergent operation due to the high risk of mortality with early operative intervention and recommended initial conservative management. After 48 hours, a repeat CTA showed increased size of the PsA (figure 2). The patient chose to be managed medically and eventually passed away 8 days after presentation. Discussion: This patient had a contained LV rupture as a STEMI complication. The CTA showed LV rupture and thrombolysis was avoided. Echo confirmed the diagnosis. This case highlights 1) the utility of imaging in in the diagnosis of LV rupture as it is usually limited by early mortality, and 2) its role in differentiating PsA from true aneurysm, which is characterized by a contained wall rupture while true aneurysms develop due to a weakened, but intact, wall.
Abstract 10450: Interleukin-17A-Correlated Myocarditis in Patients With Psoriasis
Authors: Andrea Frustaci, Maria Alfarano, Antonio Richetta, Romina Verardo, Felicita Scura, Giulia Bagnato, Rossella Scialla, Cristina Chimenti
Journal: Circulation (2022)

Background. Psoriasis is a common immune-mediated disease of the skin with possible extension to joints, aorta and eye. Myocardial inflammation has been rarely suggested. However, its incidence and pathologic mechanism have not been elucidated so far. Methods. One hundred consecutive patients (62M/38F, mean age 55 ± 13.7 years) with psoriasis were screened for cardiac involvement. Among them, five male patients (mean age 56 ± 9.5 years) showed a dilated cardiomyopathy (LVEF &lt; 40%) with normal coronary arteries and valves, and underwent a left ventricular endomyocardial biopsy for evaluation of myocardial substrate. Endomyocardial samples were processed for histology and immunohistochemistry, including myocardial expression of Toll-Like Receptor 4 (TLR4) and interleukin-17A (IL-17A), which plays a major role in psoriasis pathogenesis. Real-time PCR for cardiotropic viruses and Western blot analysis for myocardial expression of IL-17A were also performed. As controls for IL-17A expression, myocardial samples from 10 male patients with inflammatory cardiomyopathy and no psoriasis were included. Patients’ sera were tested for anti-heart autoantibodies. Results. An active lymphocytic myocarditis was revealed in all 5 patients, characterized by absence of viral genomes at PCR, positive anti-heart autoantibodies, overexpression of TLR-4 and of IL-17A at both immunohistochemistry (Figure 1A vs 1B) and Western blot analysis (mean value 44 ± 6.7 vs 12 ± 61.9 in patients with no-psoriatic myocarditis and 4± 1.5 in normal controls; Figure 1C). Conclusion. Interleukin-17A-related myocarditis can occur in up-to 5% of patients with psoriasis. It manifests as a progressive dilated cardiomyopathy that can potentially benefit from immunosuppression or monoclonal antibodies as the skin disease.
Abstract 10491: Drug-Coated Balloon and Drug-Eluting Stent Safety in Patients With Femoropopliteal and Severe Chronic Kidney Disease
Authors: Jonathan Hanna, Kim G Smolderen, Yulanka Castro-Dominguez, Gaelle Romain, Megan Lee, Jeffrey Turner, Carlos Mena-Hurtado
Journal: Circulation (2022)

Background: Severe-stage chronic kidney disease (CKD) patients were excluded from femoropopliteal disease trials evaluating drug-coated balloons (DCB) and drug-eluting stents (DES) vs. plain balloon angioplasty (POBA) and bare metal stents (BMS). We examined the interaction between CKD status and device type for the association with 24-month all-cause mortality and major amputation risk. Methods: We studied patients undergoing femoropopliteal interventions (9/2016-12/2018) from Medicare-linked VQI registry data. We compared outcomes for: (1) early-stage CKD (stages 1-3) receiving DCB/DES, (2) early-stage CKD receiving POBA/BMS, (3) severe-stage (4-5) CKD receiving DCB/DES, (4) severe-stage CKD receiving POBA/BMS. Results: We studied 8,799 patients (early-stage CKD: 94%; severe-stage: 6%). DCB/DES use was 57% vs. 51% in early-stage vs. severe-stage CKD patients. Twenty-four-month mortality risk for early-stage CKD patients receiving DCB/DES (reference group) was 21% vs. 28% (HR=1.47, 95% CI, 1.31-1.65) for those receiving POBA/BMS; severe-stage CKD patients: those receiving DCB/DES had a 49% (HR=2.61,95% CI, 2.06-3.31) mortality risk vs. 52% (HR=3.64, 95% CI, 2.91-4.55) for those receiving POBA/BMS (interaction P&lt;0.001) ( Figure ). Adjusted analyses attenuated these results. For severe-stage CKD, DCB/DES vs. POBA/BMS mortality risk was not significant at 24 months (post hoc comparison P=0.06) but was higher for POBA/BMS group at 18 months (post hoc P&lt;0.05). Early-stage CKD patients receiving DCB/DES had the lowest 24-month amputation risk (6%), followed by 11% for early-stage CKD-POBA/BMS, 15% for severe-stage CKD-DCB/DES, 16% for severe-stage CKD-POBA/BMS (interaction P&lt;0.001). DCB/DES vs. POBA/BMS amputation rates in severe-stage CKD patients did not differ (post hoc P=0.820). Conclusion: DCB/DES vs. POBA/BMS use severe-stage CKD patients was associated with lower mortality and no difference in amputation outcomes.
Abstract 10588: Pre-Clinical Study of Induced Pluripotent Stem Cell-Derived Cardiomyocyte Sheet Transplantation for a Cynomolgus Macaque Model of Doxorubicin-Induced Dilated Cardiomyopathy
Authors: Tsubasa Mikami, Takuji Kawamura, Masaro Nakae, Kota Suzuki, Eiraku Seiko, Akima Harada, Shigeru Miyagawa
Journal: Circulation (2022)

Introduction: Due to the serious shortage of cardiac donors in Japan, there is a strong demand for an effective alternative treatment to heart transplantation (HTx) and left ventricular assist device for end-stage severe heart failure. We have conducted induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) sheet transplantation for ischemic cardiomyopathy as first in human clinical trial (jRCT2053190081), based on several pre-clinical studies suggesting both of angiogenic effects and mechanical contribution of iPSC-CMs. Then, we are next aiming to expand the indication for dilated cardiomyopathy (DCM), which is the most common indication for HTx worldwide. In this study, we established a cynomolgus macaque model of Doxorubicin (Dox)-induced DCM and performed the iPSC-CM sheet transplantation. Methods: Twelve male cynomolgus macaques were treated with Dox to induce DCM every two weeks for three consecutive days in three different doses. The cardiac function was assessed over time by transthoracic echocardiography (TTE) and the effect of doxorubicin on the myocardium was investigated with histological analysis. After the establishment of animal model, we performed the iPSC-CM sheet transplantation and assessed the postoperative cardiac function by TTE and cardiac computed tomography (CT). Results: Each Two macaques treated with high (1.2 kg/mg/day) and medium (1.0 kg/mg/day) dose of Dox died before the establishment of animal model. Of the remaining eight macaques in the low dose (0.8 kg/mg/day) group, six had progressively decreased cardiac function. Histology revealed vacuolization in the left ventricle of the Dox-treated heart. Postoperative evaluation two weeks after iPSC-CM sheet transplantation revealed the improvement in cardiac function on TTE and cardiac CT (left ventricular ejection fraction: from 22 % to 31%, and from 19 % to 31 %, respectively). Conclusions: Three-month administration of low-dose Dox was able to create a cynomolgus macaque model of Dox-induced DCM with relatively high reproducibility. IPSC-CM sheet transplantation may have the possibility for improving cardiac function of DCM.
Abstract 10960: The Thoracic Duct is Well-Visualized on 3D-BSSFP Imaging in Patients With Fontan Circulation and Its Size and Tortuosity Are Associated With Worse Outcomes
Authors: Daniel A Castellanos, Sidra Ahmad, Nicole St. Clair, Lynn A Sleeper, Minmin Lu, David N Schidlow, Rahul Rathod, Suellen M Yin, Jesse Esch, David Annese, Andrew J Powell, Luis Quinonez, Raja Shaikh, Sunil J Ghelani
Journal: Circulation (2022)

Introduction: Lymphatic complications are common in patients with Fontan circulation. 3D balanced steady-state free precession (3D-bSSFP) angiography by cardiovascular magnetic resonance (CMR) is widely adopted for cardiovascular anatomical assessment. We sought to determine the frequency of thoracic duct visualization using 3D bSSFP images and assess whether thoracic duct characteristics are markers of poor clinical outcomes. Methods: This was a retrospective, single-center study of patients with Fontan circulation who underwent CMR. Patients with repaired tetralogy of Fallot (rTOF) were included as a comparison. Thoracic duct characteristics included maximum diameter and a qualitative assessment of tortuosity (Figure). Clinical outcomes included protein-losing enteropathy (PLE), plastic bronchitis, listing for heart transplant, or death. A composite outcome was defined as presence of any of the above. Results: The study group was comprised of 189 Fontan patients and 36 rTOF patients (median age at CMR 16 years, IQR: 11-23 years). The thoracic duct diameter was larger (median 2.50 vs 1.95 mm, p&lt;0.01) and more often well-visualized (65% vs 22%, p&lt;0.01) in Fontan patients vs the rTOF group. The thoracic duct diameter was larger in Fontan patients with PLE (median 4.0 vs 2.5 mm, p=0.02) vs Fontan patients without PLE, and was more tortuous in Fontan patients with congestive heart failure (CHF) vs Fontan patients without CHF (moderate or greater tortuosity in 75% vs 28.5%, p=0.02). Larger thoracic duct diameter was associated with a lower ejection fraction (R= -0.24, p&lt;0.01). The composite outcome was present in 6% of Fontan patients and was not associated with thoracic duct diameter (p=0.72) or tortuosity (p=0.09). Conclusions: The thoracic duct can be well visualized in 2/3 of patients with Fontan circulation on 3D-bSSFP images. Larger thoracic duct dimension and increased tortuosity are associated with co-morbidities experienced by Fontan patients.
Abstract 10330: Do Radiofrequency and Cryoballoon Pulmonary Vein Isolation Induce Similar Rates of Pericardial Inflammation?
Authors: John Schanz, Jonathan Wang, Daniel R Frisch, Behzad B Pavri
Journal: Circulation (2022)

Introduction: Pericardial inflammation/irritation (P I/I ) is a known occurrence after Radiofrequency (RF) and Cryoballoon (CB) pulmonary vein isolation (PVI) for pts with AF. We hypothesized that any new pericardial effusions (PE) or ECG evidence of pericarditis were clinical manifestations of P I/I post-PVI. Data comparing the incidence and clinical significance of P I/I between the 2 treatment modalities are limited. Methods: Retrospective analysis of post-PVI P I/I in pts undergoing either CB or RF ablation for AF. We included any degree of new PE or ECG changes consistent with pericarditis seen post-procedure as a surrogate for P I/I . Results: A total of 224 pts (70 CB and 154 RF) with AF undergoing their first PVI were studied. Compared to RF, CB pts tended to be female (47.1% vs 31.2%, P=0.021), were less likely to receive concurrent cavotricuspid-isthmus (CTI) ablation (4.29% vs 61.0%, P&lt;0.01), and were less likely to receive post-PVI NSAIDs (17.1% vs 56.5%, P&lt;0.01). Despite differences in baseline characteristics, the incidence of post-PVI P I/I between CB and RF was similar (17.1% vs 20.8%, P=0.469). No episode of P I/I led to any hemodynamic instability or required intervention. Pts with P I/I were more likely to be female (52.3% vs 32.4%, P=0.014) and had lower BMIs (28.7kg/m 2 vs 31.2kg/m 2 , P=0.012). Characteristics of pts in each treatment group as well as pts with and without P I/I were summarized in Table 1. Conclusions: In contrast with prior studies that demonstrated lower rates of P I/I with CB, we demonstrate similar rates of P I/I with CB and RF. The occurrence of P I/I was not associated with increased incidence of early AF recurrence. P I/I was more likely to develop in female pts with lower BMI. Although NSAIDs are often used post-PVI, we found no association between NSAID use and development of P I/I .
Abstract 10549: American Heart Association's Life's Simple 7 and Major Bleeding in Atrial Fibrillation: A Multicenter Cohort Study
Authors: Robert P Leung, Parth Visrodia, Darleen Lessard, Eric Ding, Jane Saczynski, David D McManus, Weijia Wang
Journal: Circulation (2022)

Background: Stroke prevention with oral anticoagulation (OAC) is a mainstay therapy in atrial fibrillation (AF) but is associated with increased bleeding. Identifying health determinants that contribute to this risk is essential to minimizing these adverse events and evaluating the risk benefit of OAC in an individual patient. This study examines the association between the seven cardiovascular risk factors (blood pressure, cholesterol, smoking status, physical activity, glucose, BMI, and diet) from the American Heart Association’s (AHA) Life’s Simple 7 (LS7) and major bleeding in older individuals with AF on OAC. Methods: In this multicenter prospective cohort study, we enrolled 1064 patients who were 65 years old and above, had non-valvular AF, and on OAC and followed them for 2 years. Based on AHA’s LS7 criteria, each risk factor was graded on a 3-point scale: 0 points (poor), 1 point (intermediate), and 2 points (ideal). Patients were separated into poor (0-6 pts), intermediate (7-9 pts), or ideal (10-14 pts) cohorts based on their aggregate score. Cox models were used to assess the relationship between the aggregate cohort scores and major bleeding as well as each individual cardiovascular risk factor score and major bleeding. Results: Our 1064 patients were separated into poor (n=242), intermediate (n=581) and ideal (n=241) cardiovascular health cohorts. There was a total of 95 major bleeding events, 8.93% of patients who had a major bleed, and a crude rate of 4.68 major bleeding events per 100 person-years. Compared to the ideal group, patients in the poor (HR, 2.29; 95% CI, 1.13 to 4.65) and intermediate groups (HR, 2.17; 95% CI, 1.14 to 4.14) were more likely to have a major bleeding event. Additionally, patients with poor smoking status (HR, 2.78; 95% CI, 1.29 to 5.98) or physical activity (HR, 1.66; 95% CI, 1.07 to 2.59) were significantly more likely to have a major bleeding event than those in the intermediate and ideal categories. Conclusions: In older adults with AF on OAC, poor cardiovascular health, smoking, and poor physical activity are all associated with a higher risk of major bleeding. Further investigation is needed to determine if smoking cessation and physical activity can lead to clinically meaningful reduction in bleeding events.
Abstract 10765: Association Between Prehospital Nitroglycerin and Clinical Outcome in Acute Coronary Syndrome
Authors: Soichi Komaki, TATSUYA TOKAI, Ryota Kaichi, Masafumi Takae, Takayuki Mori, Reiko Toida, Kazumasa Kurogi, Nobuyasu Yamamoto, Kenichi Tsujita, Toshihiro TSURUDA, Koichi Kaikita
Journal: Circulation (2022)

Introduction: Whether prehospital Nitroglycerin use is associated with major adverse cardiac events (MACE) remains unknown in the era of primary percutaneous coronary intervention (PCI) using stents. Hypothesis: We hypothesized that prehospital Nitroglycerin use would be associated with MACE in acute coronary syndrome (ACS) patients who underwent primary PCI. Methods: This retrospective observational study enrolled 947 consecutive patients who received the emergent PCI. Patients were classified into the two groups, with and without prehospital Nitroglycerin use. 250 patients were given prehospital Nitroglycerin sublingually or via oral spray or intravenously. The clinical outcome was MACE defined as a composite of all-cause death, myocardial infarction, and stroke at a one-year follow-up. Results: The Systolic blood pressure at the emergency department was 132 (105, 141) mmHg in the prehospital Nitroglycerin, and 135 (113, 158) mmHg in the non-Nitroglycerin group (P &lt; 0.001). Kaplan-Meier survival curves revealed that the MACE frequency was higher in the prehospital Nitroglycerin group (p = 0.021). Multivariate Cox regression analysis revealed that the prehospital Nitroglycerin use (hazard ratio, 1.65; 95% confidence interval [CI], 1.02-2.65; p = 0.002) was an independent predictor for MACE. Prehospital Nitrogricerin use, Killip classification, and Ejection fraction models resulted in a c-statistic with a statistically significant 95% PI and moderate discriminative performance (c-statistic=0.763; 95% CI, 0.7111-0.816, p&lt;0.001). Conclusions: The present results suggested that the prehospital Nitroglycerin use might worsen the one-year prognosis in ACS patients undergoing primary PCI.
Abstract 10909: A Novel ATP Citrate Lyase-Dependent Metabolic-Transcriptional Axis in Pulmonary Arterial Hypertension
Authors: Sebastien Bonnet, Charlotte Romanet, Yann Grobs, Sarah-Eve Lemay, Alice Bourgeois, Sandra Breuils-bonnet, Sandra Martineau, MABROUKA SALEM, Francois Potus, Steeve Provencher, Olivier Boucherat
Journal: Circulation (2022)

INTRODUCTION: Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary artery smooth muscle (PASMC) proliferation and suppressed apoptosis. In cancer, the sustainability of this phenotype required metabolic adaptation (Warburg effect / lipid synthesis) influencing chromatin structure and gene expression. By producing Acetyl coA the ATP Citrate Lyase (ACLY) has emerged as a key player in cancer by favoring Warburg effect, lipid synthesis and histone acetylation. We hypothesized that ACLY is upregulated in PAH and supports PAH-PASMC proliferation and contributes to PA remodelling. METHODS/RESULTS: The implication of ACLY in PAH was demonstrated by 1) an upregulation (n=10 p&lt;0.05) of its expression, activation (P-ACLY) and nuclear localization in human PAH lungs, PASMCs and experimental PAH models (sugen/hypoxia, Su/Hx rats and mice) compared to control (immunoblot/immunofluorescence); 2) mice with ACLY deleted in SMCs did not develop Su/Hx-induced PA remodelling and PAH (n=20 p&lt;0.05). Mechanistically, ACLY inhibition (siRNA/BMS) decreased proliferation (Ki67/PCNA) and increased apoptosis (AnnexinV / Survivin) in PAH-PASMCs (n=8 p&lt;0.05). These effects were associated with the inhibition of multiple genes linked to cell cycle, metabolism and lipid synthesis (RNAseq p&lt;0.05 n=6) leading to a decrease (p&lt;0.05) in Warburg effect (LDH, PKM2, P-PDH) and an increase in OCR/ECAR (seahorse). These findings were coupled with an inhibition of the histone acetyl-transferase P300 and histones H3/H4 acetylation. Motif enrichment analyses of transcriptomic datasets identified NFY, NFAT and FOXM1 (all involved in PAH and P300 regulated) as putative transcription factors implicated in ACLY-dependent gene regulation in PAH. This will be confirmed by CHIPseq/ATACseq. In vivo, effects of ACLY inhibitors (BMS/ETC1002) were assessed in rats with Su/Hx-PAH. Both decreased PA pressure, resistance, wall thickness and improved right ventricular functions (n=20; p&lt;0.05) (Echo/catheterization). CONCLUSION: We uncovered a novel ACLY-dependent metabolic-transcriptional axis explaining how PASMCs proliferate and survive in PAH. ACLY inhibition is an attractive therapeutic strategy to improve PAH as ETC1002 is clinically advanced.